Vaccines against intracellular pathogens using antigens encapsulated within biodegradable-biocompatible microspheres

Abstract

This invention relates to parenteral and mucosal vaccines against diseases caused by intercellular pathogens using antigens encapsulated within a biodegradable-biocompatible microspheres(matrix).

1. An immunostimulating composition comprising encapsulating  encapsulated microspheres comprised of (a) a biodegradable-biocompatible poly(DL-lactide-co-glycolideas  poly(DL-lactide-co-glycolide) as the bulk matrix produced by a solvent evaporation process wherein the molecular weight of the copolymer is between 4,000 to 100,000 daltons and (b) an immunogenic substance consisting of a conformationally native subunit of chronic intracellular pathogen which, in the course of natural infection with that pathogen, is exposed to the host immune system on the surface of free pathogen and/or pathogen-infected cells. 
     
     
       2. The immunostimulating composition described in  claim 1  wherein the immunogenic substance is an antigen and the antigen is pre-encapsulated into a conformationally stabilizing hydrophilic matrix consisting of an appropriate mono, di- or tri-saccharide or other carbohydrate susbstance  substance by lyophilization prior to its final encapsulation into the PLG microsphere by a solvent extraction process employing acetonitrile as the polymer solvent, mineral oil as the emulsion's external phase, and heptane as the extractant. 
     
     
       3. The immunostimulating compositions  composition described in claims  claim  1  or  2   wherein the immunogenic substance is a native (oligomeric)HIV-1 envelope antigen that is conformationally stabilized by the polymer matrix and serves to elicit in animals the production of HIV specific cytotoxic T lumphocytes  lymphocytes and antibodies preferentially reactive against native HIV-1 envelope antigen. 
     
     
       4. The immunostimulating compositions  composition described in  claim 3  wherein the amount of said immunogenic substance within the microcapsule comprises between 0.5% to 5.0% of the weight of said composition. 
     
     
       5. The immunostimulating compositions describe  composition described in  claim 4  wherein the relative ratio between the amount of the lactide:glycolide components of said matrix is within the range of 52:48 to 0:100. 
     
     
       6. The immunostimulating compositions  composition described in  claim 5  wherein the molecular weight of said copolymer is between 4,000 to 50,000 daltons. 
     
     
       7. A vaccine consisting of a blend of the immunostimulating compositions described in claims  5  or  6   composition of  claim 5 . 
     
     
       8. The immunostimulating compositions  composition described in  claim 5 , employed as a parentally  parenterally administered vaccine wherein the diameter size range of said vaccine microspheres lies between 1 nanometer and 20 microns. 
     
     
       9. The immunostimulating compositions  composition described in  claim 5 , employed as a mucosal vaccine wherein the size of more than 50% (by volume) of said vaccine microspheres is between  5 microns  to 10 microns in diameter. 
     
     
       10. A composition in accordance with  claim 1  wherein the microspheres further contain a pharmaceutically-acceptable adjuvant. 
     
     
       11. A vaccine consisting of a blend of the immunostimulating compositions described in claims  5  or  composition of  claim 6 . 
     
     
       12. The immunostimulating compositions  composition described in  claim 6  employed as a parentally  parenterally administered vaccine wherein the diameter size range of said vaccine microspheres lies between 1 nanometer and 20 microns. 
     
     
       13. The immunostimulating compositions  composition described in  claim 7  employed as a parentally  parenterally administered vaccine wherein the diameter size range of said vaccine microspheres lies between nanogram nanometer and 20 microns. 
     
     
       14. The immunostimulating compositions  composition described in  claim 6  employed as a mucosal vaccine wherein the size of more than 50% (by volume) of said vaccine microspheres is between  5 microns  to 10 microns in diameter.